Principal Investigator/Program Director (Last, First, Middle): Patterson, Steven E. Project Summary/Abstract The risk of cyanide use in a terrorist attack resulting in a mass casualties is genuine and cyanide is included on the Chemical Threat Risk Assessment (CTRA) list. In response the NIH CounterACT charge to develop effective medical countermeasures, this project is focused on development of an effective drug/device combination to deliver our rapidly acting antidote, sulfanegen, to victims of cyanide exposure. We have previously demonstrated that sulfanegen, a novel cyanide antagonist discovered in our labs, (Patterson, Center for Drug Design) is effective in reversing lethal cyanide toxicity in murine, swine and rabbit models of cyanide exposure. Our demonstration of sulfanegen?s efficacy includes dose optimization, pharmacokinetics, species justification, formulation optimization, and safety assessment. In order to furthere develop our countermeasure, Windgap Medical?s autoinjector design will be customized to accommodate sulfanegen?s dosing characteristics. The Windgap Medican-Minnesota consortium?s ultimate goals are to 1) obtain an IND/IDE from the FDA, 2) conduct clinical trials and 3) FDA approval under the animal rule. The focus of this proposal is therefore on development of an optimized combined autoinjector/sulfanegen lead, demonstration of this lead?s efficacy and safety in non-GLP studies according to PAR-16-331, and establish the basis for a later round of funding under BARDA that will allow IND enabling studies.